Drug resistance in tuberculosis appears to have reached a peak in several patients in India, who are virtually untreatable with available medications.

Drug resistance in tuberculosis appears to have reached a peak in several patients in India, who are virtually untreatable with available medications.

In a letter to Clinical Infectious Diseases, published online, Mumbai physicians described four patients whose TB was resistant to five front-line drugs and seven second-line medications.

They are "totally drug-resistant," according to Zarir Udwadia, MD, and colleagues at P. D. Hinduja National Hospital and Medical Research Centre in Mumbai.

Udwadia and colleagues blamed the rise of such resistance on India's healthcare system, which has had some success against normal TB, but which they said does not pay enough attention to resistant strains.

As a result, many patients with resistant TB go to private physicians who are "unregulated both in terms of prescribing practice and qualifications," they said.

The result is inadequate care that leads to increasing resistance, rather than cure, they argued.

The emergence of resistance to all available TB drugs "is not surprising," according to Kenneth Castro, MD, director of the CDC's Division of Tuberculosis Elimination.

The goal now, he told MedPage Today in an email, should be to stop it from happening to a greater extent

"We must ensure treatment adherence to minimize interruption," he said. "We must also ensure the selection and use of appropriate drug regimens (and) rapid diagnostics so that people with drug resistant TB are started on the correct regimens at the right time."

The four patients are the first in a series of 12 cases that have emerged since doctors at the institution began grappling with "increasingly resistant strains of tuberculosis" a few years ago, Udwadia and colleagues reported.

TB treatment is usually relatively easy -- the bacterium in most cases succumbs to a regimen consisting of isoniazid (Nydrazid), rifampin (Rifadin), ethambutol (Myambutol), and pyrazinamide for eight weeks, followed by isoniazid and rifampin for another 18 weeks.

But inadequate or interrupted treatment can lead to resistance, which has been quantified as multidrug-resistant (or MDR-TB) and extensively drug-resistant (XDR-TB).

MDR-TB is resistant to isoniazid and rifampin, although other first-line drugs and several second-line drugs remain available.

XDR-TB is resistant to isoniazid and rifampin, as well as any fluoroquinolone and at least one of three injectable second-line drugs, such as amikacin (Amikin), kanamycin (Kantrex), or capreomycin (Capastat).

The four patients reported by Udwadia and colleagues were resistant to isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin -- the standard first-line drugs -- as well as ofloxacin (Floxin), moxifloxacin (Avelox), kanamycin, amikacin, capreomycin, para-aminosalicylic acid, and ethionamide (Trecator).

In three of the cases, the researchers conducted a careful analysis of their prescriptions and found that, in an effort to cure their MDR-TB, each had been given "erratic, unsupervised second-line drugs, added individually and often in incorrect doses, from multiple private practitioners" over an 18-month period.

The resulting resistance, Udwadia told reporters, was "a given."

He and his colleagues noted that the World Health Organization estimates that India accounts for about 20% of the world's burden of MDR-TB -- more than 110,000 cases in 2006.

Although the WHO does not have a category of totally drug-resistant TB, such cases have also been reported in Iran.

In the U.S., the CDC's Castro said, resistant TB is about 1% of cases, but "it does pose a serious threat to our ability to treat and control TB."

Indeed, in 2009, U.S. doctors reported a single case of what they called extensively drug-resistant TB - or XXDR-TB -- in a Florida man. In that case, a man who had surprisingly never been treated for the disease was diagnosed with a strain that was resistant - like those in India - to all first- and second-line drugs.

Eventually, with the aid of a wide variety of experimental therapies, the man was cured.

"We have seen TB resistant to all drugs in the U.S., but fortunately, have still been able to keep TB drug resistance under control," Castro said.

But the Indian cases "remind us of the global nature of TB," he added. "TB knows no boundaries and can easily spread across countries."

The authors did not report external support for the study or any conflicts.

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